Bladder cancer (BC) is a complex and highly heterogeneous stem cell disease associated
with high morbidity and mortality rates if it is not treated properly. Early diagnosis with personalized
therapy and regular follow-up are the keys to a successful outcome. Cancer stem cells (CSCs) are
the leading power behind tumor growth, with the ability of self-renewal, metastasis, and resistance
to conventional chemotherapy. The fast-developing CSC field with robust genome-wide screening
methods has found a platform for establishing more reliable therapies to target tumor-initiating
cell populations. However, the high heterogeneity of the CSCs in BC disease remains a large issue.
Therefore, in the present review, we discuss the various types of bladder CSC heterogeneity, important
regulatory pathways, roles in tumor progression and tumorigenesis, and the experimental culture
models. Finally, we describe the current stem cell-based therapies for BC disease.